Part 1. Overview Information

Key Dates

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

The 4D Nucleome (4DN) NIH Common Fund Program was launched in 2015 with the goal of developing the tools and resources that would enable the characterization of the three-dimensional structure and dynamics of human and mouse genomes and provide deeper mechanistic insights into how the nucleus is functionally organized. The impetus for its selection as a Common Fund program was the growing awareness that understanding the architecture of the cell nucleus may have widespread and profound implications for human health and disease, but our ability to study nuclear organization was hindered by technological and conceptual challenges.

Key deliverables from the initial 5 years of support include: 1) next-generation genome analysis, imaging and computational tools to explore nuclear organization and its relationship with the regulation of gene expression programs, including in single cells; 2) pilot reference maps of the 3D architecture of the interphase nucleus for a select set of eukaryotic cells; 3) validated predictive models of genome conformation/function relationships; 4) first-generation tools to explore nuclear dynamics through controlled disruption of nuclear architecture and imaging of reporter loci in live cells and tissue, and 5) first-generation community data and metadata standards for the most commonly used 4DN technologies and protocols (https://www.4dnucleome.org/).

A number of outstanding questions and technological challenges remain. These include: 1) better means of studying chromatin dynamics in live cells and in complex tissues, which will likely imply a heavier reliance on high-content imaging-based approaches and methods to distill massive amounts of imaging data; 2) better tools for the controlled disruption of nuclear features to better understand structure/function relationships in dynamic experimental systems; 3) tools to explore molecular components of the functional nuclear architecture that are still undefined, including protein complexes, non-coding RNAs, and the composition and organization of nuclear bodies, compartments and microenvironments; and 4) development of next-generation analytical, visualization and modeling tools that would be accessible and usable by the broader scientific community and could lead to reliable 4D models of genome organization.

These outstanding scientific and technology challenges can be met through the creation of a research environment that promotes multidisciplinary approaches, team science and data integration. The ultimate goal for this endeavor is to deliver data and tools to be used by the broader community to address the role of nuclear organization in health and disease and in lifespan. The proposed Phase 2 is designed to achieve these goals through the following six initiatives, of which this FOA is one:

• RFA-RM-20-003 Real-Time Chromatin Dynamics and Function (U01 Clinical Trial Not Allowed)
• RFA-RM-20-004 4DN Centers for Data Integration, Modeling and Visualization (UM1 Clinical Trial Not Allowed)
• RFA-RM-20-005 4DN Organization and Function in Human Health and Disease (U01 Clinical Trial Not Allowed)
• RFA-RM-20-006 New Investigator Projects on 4DN Organization and Function in Human Health and Disease (U01 Clinical Trial Not Allowed)
• RFA-RM-20-007 Limited Competition: 4DN Organizational Hub (U01 Clinical Trial Not Allowed)
• RFA-RM-20-008 Limited Competition 4DN Data Coordination & Integration Center (U01 Clinical Trial Not Allowed)

Awards funded under these FOAs are anticipated to pursue research activities conducted by multidisciplinary teams of investigators. Awardees from all 6 initiatives will form the 4DN Network, with the overarching goal of understanding the role of nuclear organization in health and disease and in lifespan. Validation and comparisons across studies will be essential to achieve this goal so investigators must be willing to work collaboratively as part of the Network.

Research Objectives and Areas of Interest

Progress applying 4DN tools to human health and disease has been hampered by the need for such studies to use more challenging systems such as human primary cells, tissues, or organoids. The purpose of this Funding Opportunity Announcement is to support projects that apply new or existing tools to monitor and/or manipulate the 4D nucleome in the context of human health and disease. Areas of potential scientific focus include but are not limited to: enabling monitoring and manipulation of 4DN features in vivo; exploring the stability/lability/reversibility of nucleome changes; studying transcriptional and non-transcriptional functional consequences; and promoting strategies to investigate the nucleomes of cell types within heterogenous tissues using single cell, spatial genomics, and other approaches. All applications must set aside 20% of their Direct Costs from years 2-5 of the award to support new collaborative research opportunities in consultation with NIH staff. These projects are anticipated to further both the needs of the funded project and the 4DN consortium.

Specific Areas of Research Interest

Applications that are not responsive to this RFA will not be reviewed. In order to be responsive to this FOA:

• The primary thrust of the application MUST be to apply new or existing tools to monitor and/or manipulate 4D nucleome organization in the context of human health and disease. Any human disease or biological process relevant to NIH’s mission may be proposed. Relevant processes include but are not limited to: environmental exposures (e.g. addictive substances, toxins, psychosocial stress), development, life span and aging, pathogenesis, circadian rhythms, reproductive cycles, and sleep/wake cycles. Projects proposing to study processes involved in resilience and recovery may also be responsive. The 4D nucleome includes spatial and temporal changes over time related to chromatin conformation, structures within the nucleus (e.g. nuclear bodies, nuclear pore, biomolecular condensates), or their interactions
• At least one Specific Aim MUST propose to use human primary cells, tissues, organoids, or xenografts to understand human health and disease, unless human tissue is difficult or impossible to obtain (e.g. embryo, brain, heart, bone). In such cases the applicant instead may propose to use mammalian tissues if the applicant can justify how the proposed work would facilitate transition to the study of human tissues in the future. The human primary cells, tissues, organoids, or xenografts proposed should be directly relevant to the disease or biological process being studied.
• Although applications composed entirely of computational approaches will not be responsive to this FOA, applications with computational, data analysis, or modeling components are encouraged.
• No more than 25% of the budget may be proposed to be used for the development of new technologies.

Select research examples include but are not limited to:

• Identification of changes in chromosome structural features in health and disease including through pathogenesis, development, life course, or environmental perturbations.
• Comparison of nuclear organization in cell types or tissues from diseased and healthy individuals.
• Interrogation of 4DN structures using genomic, imaging, and/or biophysical methods to understand 4DN differences between healthy and diseased tissu?e.
• Monitoring and/or manipulation of nuclear organizational features in vivo.
• Interrogation of functional consequences of 4DN structural features with respect to gene expression in the context of human health and disease.
• Interrogation of functional consequences of 4DN structural features with respect to DNA replication, DNA repair, or chromosome segregation in the context of human health and disease.
• Interrogation of the significance of chromosome structural features to other aspects of nuclear organization, including chromosomal territories, nuclear bodies, biomolecular condensates, etc.in the context of human health and disease.
• Integration of nucleomic, imaging, and biochemical approaches to allow a better understanding of 4DN changes over time in the context of human health and disease.
• Investigation of the relationship between SNPs linked to human health and disease and 4D nucleome structural features.

Some examples of non-responsive applications are:

• Applications that focus on general 4DN mechanisms with no health or disease context. Such applications may be appropriate for other 4DN Funding Opportunity Announcements mentioned above or investigator-initiated studies.
• Proposals that do not include one aim or sub-aim proposing to use human primary cells or tissues or that do not appropriately justify the use of non-human mammalian cells or tissues.
• Applications that propose to use surrogate human tissues (e.g. blood) not directly related to the human disease or biological process proposed for study.
• Applications proposing only computational or modeling approaches?.

It is anticipated that applications supported by this RFA will include strong interdisciplinary collaborations between 4D nucleome experts and human health or disease researchers. While preliminary data showing they are technically able to carry out the proposed experiments may be beneficial, pilot preliminary data is not required. Applicants proposing very high risk studies may choose to request smaller budgets and/or shorter periods of support (e.g. 2 or 3 years rather than 5 years). Program staff anticipate recommending a set of scientifically diverse projects for funding given that this RFA covers all NIH-relevant human health and disease processes

Consortium Responsibilities

This FOA uses the U01 Cooperative Agreement mechanism. Successful applicants will become members of the larger 4D Nucleome Consortium composed of investigators who have been funded in response to at least one of the six related 4DN Network FOAs. In addition to completing the research goals outlined in their applications, successful applicants will be expected to work collaboratively with all members of the 4D Nucleome Network, including the 4DN Network Organizational Hub (RFA-RM-20-007) and the 4DN Network Data Coordination & Integration Center (RFA-RM-20-008), to help develop common standards, metrics for data generation and storage, and data analysis and visualization tools that can be used by the broader scientific community. The 4DN Network will encourage the initiation of new collaborative research projects across the entire network.

A key aspect of this program is the formation of a consortium-type partnership amongst all 4DN Network awardees. Shared responsibilities derived from the use of the cooperative agreement mechanism are described later in this FOA, and will be further articulated during the kickoff meeting of the 4DN Network that will take place a few months after awards are made. All 4DN Network investigators will be required to attend this initial 4DN Kickoff meeting, as well as annual 4DN investigator meetings and regular teleconferences with Network members and NIH Staff for the duration of the funding cycle.

All applicants are strongly encouraged to contact NIH Staff to discuss the alignment of their proposed work with the goals of this FOA, and the 4DN Program. A Technical Assistance teleconference will be held for potential applicants. NIH staff will be available to answer questions related to this FOA. Time, date, and dial in information for the call will be announced in an NIH Guide Notice and will be posted on the 4DN website: http://commonfund.nih.gov/4Dnucleome/index. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

• Eligible Agencies of the Federal Government

• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration , but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

John Satterlee, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1010
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

• Funds equivalent to 20% of the direct costs must be allocated to support new collaborative research opportunities in consultation with NIH staff in grant funding years 2, 3, 4 and 5. Allocated budget funds for identified projects should not exceed $80,000 in direct costs within any grant year (2-5).
• No more than 25% of the budget for the entire project period may be proposed to be used for the development of new technologies.
• In addition, applicants must budget appropriate funds to support travel of investigators to annual 4DN Consortium meetings within the continental United States.

All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

The primary thrust of the application MUST be to apply new or existing tools to monitor and/or manipulate 4D nucleome organization in the context of human health and disease. Any human disease or biological process relevant to NIH’s mission may be proposed. At least one Specific Aim MUST propose to use human primary cells, tissues, organoids, or xenografts to understand human health and disease. In cases where human tissue is difficult or impossible to obtain (e.g. embryo, brain, heart, bone), the applicant instead may propose to use mammalian tissues if the applicant can justify how the proposed work would facilitate transition to the study of human tissues in the future. The human primary cells, tissues, organoids, or xenografts proposed should be directly relevant to the disease or biological process being studied.

In addition, applicants are asked to address the following points within the Research Strategy:

1) Significance: Explain how the proposed study will transform our ability to understand the mechanisms of 4D nucleome organization and function for a particular disease or human health process (including environmental exposures or changes during development or across lifespan). Explain how this work will dramatically improve our understanding of the health or disease mechanisms or lay a strong foundation for future prevention, diagnosis, or therapeutic efforts. Describe what foundational knowledge will be provided by the study to inform the design of tools to monitor or manipulate the human health process or disease being investigated. Explain how the proposed work will advance our ability to understand and develop new therapeutic approaches to alter or treat the human health process or disease being investigated. Describe studies that, if fully successful, will transform the ability to understand the mechanisms of 4D nucleome organization and function for a particular disease or human health process (including environmental exposures or changes during development or across lifespan).

2) Investigators: Describe the expertise that the investigative team has in 4D Nucleome approaches and in the disease or human health process of interest.

3) Innovation: If development of a new technology is proposed, explain in what ways it will be significantly faster, cheaper, more sensitive, or more robust than existing technologies.

4) Approach: If only non-human tissues were proposed, describe how the proposed work would facilitate transition to the study of human tissues in the future.

Project timeline: A timeline (Gantt chart) including milestones should be provided for all studies. Milestones are goals that create decision points in the project and should include clear criteria for success. Yearly milestones should provide clear indicators of a project’s continued success or emergent difficulties and may be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. Milestones and the timeline should be provided in a separate heading at the end of the Approach section?.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• The following modifications also apply, in addition to standard NIH policies:
• All applications, regardless of the amount of direct costs requested for any one year, should include a Data Sharing Plan in the management plan of the application.
• Applicants should state that they will adhere to the 4D Nucleome sharing policies and procedures described in the "Cooperative Agreement Terms and Conditions of Award" (Section VI.2 below)
• Applicants should explicitly state their willingness to cooperate with the 4DN Program, 4DN Network Steering Committee (4DN-SC), NIH staff, and other stakeholders in the development and implementation of research and standardization methods, data standards and formats, metadata requirements, and quality control metrics for this resource.
• Protocol, tool and reagent sharing: The applicant should discuss plans for sharing and distribution of non-data resources that will be generated by the proposed project, including models, protocols, computational tools, biomaterials, and reagents. As one of the essential goals of this program, NIH intends that tools and reagents generated by the 4DN Network be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible, thus enabling downstream applications for the reagents by the larger scientific community. The 4DN-OH will work with all 4DN Network investigators to collect, curate, and disseminate information regarding critical tools and reagents being developed by the 4DN Network through the 4DN portal. Whether tools and reagents are distributed by individual investigators or through public repositories, the 4DN portal is expected to serve as a "one-stop shop" for all 4DN Network-generated tools and reagents. Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (https://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov).

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement .

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed). Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific for this FOA: How will the proposed study transform our ability to understand the mechanisms of 4D nucleome organization and function for a particular disease or human health process (including environmental exposures or changes during development or across lifespan)? How will this work dramatically improve our understanding of the health or disease mechanisms or lay a strong foundation for future prevention, diagnosis, or therapeutic efforts? What foundational knowledge will be provided by the study to inform the design of tools to monitor or manipulate the human health process or disease being investigated? How will the proposed work advance our ability to understand and develop new therapeutic approaches to alter or treat the human health process or disease being investigated?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific for this FOA: What expertise does the investigative team have in 4D Nucleome approaches and in the disease or human health process of interest?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific for this FOA: If development of a new technology is proposed, will it be significantly faster, cheaper, more sensitive, or more robust than existing technologies?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project ? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific for this FOA: Is the projected timeline feasible and appropriate? Are the proposed milestones quantitative and appropriate for each phase of the project? If only non-human tissues were proposed, how appropriate are the justification and description of how the proposed work would facilitate transition to the study of human tissues in the future? Does the team have access to the human tissues or cells required for the proposed experiments?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific for this FOA: Does the team have access to appropriate equipment required for the 4D Nucleome analysis approaches they propose to use?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA. Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS PHS, and NIH grant administration policies.

The administrative and funding instrument used for all awards in the 4DN program will be the cooperative agreement (U01 or UM1 grants), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. A Memorandum of Understanding (MOU) developed by the NIH Common Fund should serve as a guidance document to provide a framework under which relationships between investigators and NIH Program Staff are established. Templates for Confidential Disclosure Agreements (CDAs) and Collaborative Research Agreements (CRAs) have been developed by the NIH Office of Technology Transfer. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

Responsibilities of PD(s)/PI(s):

• The PD/PI will be primarily responsible for the planning and conduct of the operations defined by the terms and conditions of the cooperative agreement award.
• The PD/PI will assume responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research and administrative functions supported under this Funding Opportunity Announcement in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
• The PD/PI must operate in accordance with processes and goals as delineated in the Funding Opportunity Announcement.
• The PD/PI and his/her staff will be required to fully participate in a cooperative, interactive, and collaborative manner with NIH staff, 4DN Consortium investigators and one another.
• The PD/PI will become voting members on the 4DN Consortium Steering Committee (4DN-SC) that will be tasked with developing and updating agreements that address a variety of issues, including: (1) procedures for data sharing among consortium members, data sharing with the scientific community outside of the 4DN Consortium, and data sharing with industry partners; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the consortium as well as information and/or data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing tools and reagents under an overarching MTA amongst consortium members that operationalizes material transfer in an efficient and expeditious manner; (5) publication policy for the entire 4DN Consortium, determining timing, authorship and content of co-publications, in order to facilitate collaborations and co-publications by consortium members while protecting each 4DN investigator’s primary ownership and authorship of their data and discoveries.
• The PD/PI must operate in accordance with processes, goals, and policies established by the 4DN-SC.
• The PD/PI agrees that any industry collaborations should be governed by a research collaboration agreement (e.g. CTA, RCA, etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH policies and procedures and any policies and procedures developed by the 4DN-OH or the 4DN-SC.
• The PD/PI must attend an initial face-to-face meeting of 4DN PDs/PIs soon after all 4DN awards have been made, followed by at least one 4DN Consortium investigator meeting annually.
• The PD/PI agrees to provide milestones if requested by the NIH (typically describing annual and overall project period milestones, including data generation milestones ; usually provided at the outset of the award and annually thereafter if needed, but may also occur at other times as requested by NIH program staff).

Sharing:

• The PD/PI and his/her staff will maintain the confidentiality of the information developed or handled by the 4DN Consortium, including, without limitation, unpublished data, informatics tools, protocols, data analysis, confidential exchanges between members of the 4DN Consortium, etc. per policies approved by the 4DN-SC, as well as any confidential information received by third party collaborators.
• The PD/PI agrees to fully disclose data, algorithms, software source code, and experimental methods to the other members of the Consortium for the purpose of scientific evaluation and use by other consortium members.
• The PD/PI must facilitate the public release and dissemination of results, data, reagents, technologies, software and other resources generated through this 4DN award in a timely manner through the 4DN DCIC and the 4DN portal managed by the 4DN-OH. The PD/PI is expected to share data and resources generated through this award in accordance with the sharing policies described in this document (see below), with further sharing policies and recommendations developed and approved by the 4DN-SC, NIH sharing policies and the goals of the FOA.
• Data/software ownership and transition to another grantee: the 4DN-DCIC will host data and metadata generated by the 4DN. The awardee is responsible for the proper stewardship and security of all data. A fundamental objective of this cooperative agreement is to ensure that the valuable data and software resources remain available without interruption to the research community if awardee withdraws or otherwise can no longer manage the resource or if the award is terminated by the NIH. Consistent with 45 C.F.R. 75.322, the awardee will own the data generated and software developed by the awardee, and it will be able to continue to use these data and software upon expiration or termination of the award. NIH will have unrestricted cost-free access and use of the data and software generated by the awardee, including the right to transfer said data and/or software to other NIH-funded and/or managed resource projects, at the NIH's sole reasonable discretion upon termination or expiration of this cooperative agreement. Ownership of the data and software hosted or uploaded on the DCIC platform remain with the data and software providers. The DCIC has no possessor rights of the data and software provided or generated by its users, who will retain ownership and control of their own resources.
• Open Source Technology: capabilities and software built as part of the DCIC must be delivered under an open source model. Organizations may propose to use proprietary platforms, so long as the requirements for data transparency and interoperability are maintained.

Involvement of NIH Program Staff:

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The NIH will designate program staff, including a Program Officer and a Grants Management Specialist to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer and Grants Management Specialist will be named in the Notice of Grant Award.
• A NIH Project Scientist will be substantially involved in the management of the awards resulting from this FOA above and beyond the normal stewardship of an NIH Program Official.
• The Project Scientist may assist awardees in the development of policies for dealing with situations that require coordinated action.
• The Project Scientist may provide advice in the management and technical performance of the investigation.
• The Project Scientist may assist in promoting the availability of the data and resources developed in the course of this project to the scientific community at large.
• The NIH Project Scientist and Program Officer will review the scientific progress of 4DN projects, and review the project for compliance with sharing and operating policies developed by the 4DN-SC and the NIH. Based on this review, the Project Scientist in conjunction with the Program Officer may recommend to the NIH to continue funding, or to withhold or restrict support for the grantee for lack of progress or failure to adhere to 4DN Consortium or NIH policies. Review of progress may include regular communications between the PD/PI and NIH staff, site visits, or fiscal review. The NIH also retains the option of organizing periodic external review of progress of the work supported by the 4DN award.
• The NIH reserves the right to terminate or restrict any 4DN award in the event that work on one or more components of the project should be deferred pending completion of others, or in the event of (1) A substantial shortfall in accomplishing the management goals and responsibilities as stated in the reviewed application, (2) A failure to meet the 4DN Consortium policies and procedures, (3) Substantive changes in the management of the 4DN award that are not in keeping with the objectives of the FOA and/or (4) failure to make substantial progress towards milestones keeping in mind the agreed upon go/no-go decisions.

Areas of joint responsibilities:

4DN Consortium Steering Committee

• The awardee agrees to the role and authority of the 4DN-SC that is responsible for joint governance of 4DN Consortium activities. The main characteristics and functions of the 4DN-SC are as follows:
• The 4DN-SC will be composed of its voting members that will include one representative investigator for each of the 4DN awards resulting from RFA-RM-20-003, RFA-RM-20-004, RFA-RM-20-005, RFA-RM-20-006, RFA-RM-20-007 and RFA-RM-20-008, and one NIH Project Scientist involved in the management of the 4DN Consortium. The 4DN-OH PD/PI and 4DN-DCIC PD/PI will be permanent members of the 4DN-SC. The NIH voting member will be chosen by the NIH 4DN Working Group, that will also decide the length of the term of service. All other members of the 4DN-SC will be selected by their parent award peers to serve at least a 2-year term on the 4DN-SC. Other designated NIH program staff, 4DN-OH staff, 4DN-DCIC staff or External Program Consultants (see definition below) may attend the 4DN-SC meetings on a regular or ad-hoc basis, but will be ex officio (non-voting) members.
• The 4DN-SC will be constituted at the 4DN Consortium kick-off meeting, and will meet at least quarterly, including at least once in-person during the annual 4DN Investigator Meeting.
• The first meeting of the 4DN-SC will be chaired by the NIH representative on the 4DN-SC. Following that initial meeting, one to up to three 4DN-SC Chairpersons will be chosen by the NIH amongst the 4DN-SC to serve a two-year term. The Chairperson(s) is(are) responsible for helping NIH Staff to coordinate the 4DN-SC activities, for preparing 4DN-SC meeting agendas and for chairing 4DN-SC meetings. After two years of service, NIH staff may ask the 4DN-SC Chairperson(s) to serve a second 2-year term, or choose a replacement for that role. NIH staff may also choose to replace 4DN-SC Chairs at any time based on poor job performance or failure to follow the relevant procedures and guidelines.
• Although all major scientific and policy decisions will be determined by voting policies as established by the current 4DN-SC, it is expected that successful policies developed and implemented in Phase 1 of the program will continue and whenever necessary, be adopted during current phase of the program. These will include, but not limited to, various working group policies, data and software sharing, publication, and/or other consortium policies (4D Nucleome Portal). Early sharing with the broader scientific community of novel tools, technologies, datasets and scientific discoveries will remain the responsibility of each and all 4DN investigators. In order to do that, all investigators must adhere to the Publication Policies that will require internal sharing of planned manuscripts through a dedicated manuscript tracking system and the early public sharing of submitted manuscripts via appropriate public preprint server (such as bioRxiv, arXiv, ChemRxiv) prior to, or concurrently with the time of submission to a journal.
  Specific activities of the 4DN-SC will include, but are not limited to: developing collaborative protocols; identifying impediments to success and strategies to overcome them; developing shared tools for disseminating information about the 4DN Consortium projects; identifying opportunities for sharing techniques, materials, information and tools developed within each individual 4DN Consortium project; facilitating communication and fostering collaboration across the 4DN Consortium; reviewing progress of the 4DN Consortium towards meeting the overall Consortium goals; developing or updating policies to facilitate collaborations and co-publications by consortium members; developing or updating data standards, metadata requirements, data quality standards, and submission and release policies; ensuring the 4DN Consortium leverages existing NIH resources and programs; helping organize the scientific Agenda for the annual 4DN Investigator Meeting.
• 4DN trans-consortium subcommittees and working groups may be constituted following recommendations and approval by the 4DN-SC, to help the 4DN-SC with scientific planning activities, development of common 4DN Consortium standards and policies, etc.
• The 4DN-OH is responsible for providing and maintaining a record of minutes of all 4DN-SC meetings, which will be approved by the 4DN-SC.
• The 4DN-SC activities and decisions will consider the advice of the various trans-consortium subcommittees and working groups, and the NIH Staff.
• NIH Project Scientists involved with the management of the 4DN Consortium will help the 4DN-SC develop and draft sharing and operating policies that are in accordance with NIH guidelines. NIH Project Scientists, in concert with the 4DN-SC, will also have the option to redirect activities or operations being pursued within the 4DN-OH and 4DN-DCIC if it is considered beneficial to the overall program.
• The 4DN-OH PD/PI and 4DN-DCIC PD/PI will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the 4DN-SC. The 4DN-OH PI, the 4DN-DCIC PI, and the 4DN-SC Chair(s) will jointly report progress with regard to overall 4DN Consortium activities and the development of new 4DN Consortium policies at the annual 4DN Investigator Meeting.

4DN Data Release and Use, Software Sharing and Publication Policies:

The PD/PI agrees to follow the 4DN Data Release and Use, Software Sharing and Publication Policies as currently stated (see https://www.4dnucleome.org/policies.html), and to follow any updates to these policies that may be approved by the 4DN-SC in the future.

4DN External Program Consultants (4DN-EPCs)

An independent panel of 4-8 External Experts will be appointed on an ad hoc basis by NIH and meet by teleconference or in person with the 4DN Program Staff at least once a year. The 4DN-EPCs will be updated on progress and provide feedback to NIH on adjustments and future directions for the 4DN Network activities. NIH staff will appoint a 4DN-EPC Chair who will attend the annual 4DN Network Investigator Annual Meeting and be invited to participate ex officio in 4DN-SC meetings. All 4DN-EPCs will be given the opportunity to listen to 4DN-SC meetings and to attend the annual 4DN Network Investigator Annual Meeting. The 4DN-OH will support costs for 4DN-EPCs who wish to participate in the 4DN Network Investigator Annual Meeting.

Dispute Resolution

Disagreements that may arise in scientific/technical matters, publication/authorship matters or programmatic matters (within the scope of the award) between award recipients, or between award recipients and the NIH, may be brought to arbitration after first attempting to resolve the issue through the 4DN-SC or its subcommittees, as appropriate. An Arbitration Panel composed of three members will be convened. The Panel will be composed of: a designee of the 4DN-SC chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two members; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure in no way affects the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement. A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

John Satterlee, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1020
Email: [email protected]

David Balasundaram, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1022
Email: [email protected]

Aida Vasquez
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-2154
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.